Journal article
The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation
Journal of experimental pharmacology, Vol.2010(2), pp.83-91
07/2010
Handle:
https://hdl.handle.net/2376/108798
PMID: 20865058
Abstract
BACKGROUND: Cranberry products have been implicated in several case reports to enhance the anticoagulant effect of warfarin. The mechanism could involve inhibition of the hepatic CYP2C9-mediated metabolic clearance of warfarin by components in cranberry. Because dietary/natural substances vary substantially in bioactive ingredient composition, multiple cranberry products were evaluated in vitro before testing this hypothesis in vivo. METHODS: The inhibitory effects of five types of cranberry juices were compared with those of water on CYP2C9 activity (S-warfarin 7-hydroxylation) in human liver microsomes (HLM). The most potent juice was compared with water on S/R-warfarin pharmacokinetics in 16 healthy participants given a single dose of warfarin 10 mg. RESULTS: Only one juice inhibited S-warfarin 7-hydroxylation in HLM in a concentration-dependent manner (P < 0.05), from 20% to >95% at 0.05% to 0.5% juice (v/v), respectively. However, this juice had no effect on the geometric mean AUC(0-∞) and terminal half-life of S/R-warfarin in human subjects. CONCLUSIONS: A cranberry juice that inhibited warfarin metabolism in HLM had no effect on warfarin clearance in healthy participants. The lack of an in vitro-in vivo concordance likely reflects the fact that the site of warfarin metabolism (liver) is remote from the site of exposure to the inhibitory components in the cranberry juice (intestine).
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Details
- Title
- The warfarin-cranberry juice interaction revisited: A systematic in vitro-in vivo evaluation
- Creators
- Ngoc Ngo - UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USAScott J BrantleyDaniel R CarrizosaAngela Dm KashubaE Claire DeesDavid J KrollNicholas H OberliesMary F Paine
- Publication Details
- Journal of experimental pharmacology, Vol.2010(2), pp.83-91
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- New Zealand
- Grant note
- R01 GM077482-01A2 / NIGMS NIH HHS M01 RR000046 / NCRR NIH HHS P30 AI050410 / NIAID NIH HHS R01 GM077482 / NIGMS NIH HHS M01 RR000046-476472 / NCRR NIH HHS R01 GM077482-03 / NIGMS NIH HHS R01 GM077482-02 / NIGMS NIH HHS
- Identifiers
- 99900546948101842
- Language
- English
- Resource Type
- Journal article